Examples of treating abnormalities of brain function include the acute infusion of Gamma-amino-buturic-acid agonists into an epileptic focus or pathway to block transmission, and the chronic delivery of opiates or other analgesics infused directly to the peri-aqueductal grey matter or to thalamic targets for the treatment of intractable pain. Also, cytotoxic agents can be delivered directly into a brain tumor. Intraparenchymal infusion could also be used to deliver therapeutic agents to brain targets that could not be delivered systemically because they will not cross the blood-brain barrier. For example, the treatment of patients with Parkinson's disease, Alzheimer's disease, head injury, stroke and multiple sclerosis may be carried out by the infusion of neurotrophic factors to protect and repair failing or damaged nerve cells. Neurotrophins may also be infused to support neural grafts transplanted into damaged or malfunctioning areas of the brain in order restore function.
Intraparenchymal drug delivery has been demonstrated in non human primates and in rats. For intraparenchymal drug delivery to a human or non-human brain, it is proposed that a catheter be implanted, and the drug be pumped intermittently or continuously to the desired brain target. For long term drug delivery, a pump containing a reservoir would be implanted subcutaneously and the reservoir refilled as necessary percutaneously through a palpable port. In particular U.S. Pat. No. 6,042,579 discloses techniques for treating neurodegenerative disorders by the infusion of nerve growth factors into the brain.
In order to perform neurosurgery, the surgeon needs, in the first instance, to identify the position of the desired target. This is normally achieved by fixing a stereotactic reference frame to the patient's head which can be seen on diagnostic images, and from which measurements can be made. The stereotactic frame then acts as a platform from which an instrument is guided to a desired target using a stereoguide that is set to the measured co-ordinates. Once an instrument is guided to the desired target, treatment can begin.
A number of difficulties are encountered in such neurosurgical procedures. Sub-optimal placement of the instrument being inserted may lead to significant morbidity or treatment failure. Brain targets for treating functional disorders are usually deeply situated and have small volumes. For example, a desired target for treating Parkinson's disease is situated in the sub-thalamic nucleus and is 3-4 mm in diameter, or an ovoid of 3-4 mm in diameter and 5-6 mm in length. Other targets such as the globus palladus or targets in the thalamus are usually no more than 1-2 mm larger. For such a small target sub-optimal placement of as little as 1 mm will not only reduce the effectiveness of the treatment, but may also induce unwanted side affects such as weakness, altered sensation, worsened speech and double vision. However, functional neurosurgical targets are often difficult or impossible to visualize on diagnostic images, and so that actual position may be need to be inferred with the reference to visible landmarks in the brain and using a standard atlas of the brain to assist the process. Anatomical variations between an individual and the atlas, and even between different sides of the same brain of an individual means that placement may be sub-optimal. Other reasons for sub-optimal placement may result from patient movement during image acquisition, or geometric distortion of imaging which can be intrinsic to the images method. Also, during surgery, brain shift can occur which might result from the change in the head position from that during image acquisition to the position on the operating table, from leakage of cerebrospinal fluid when a burr hole is made with a subsequent sinking of the brain, and also from the passage of the instrument through the brain. Surgeons attempt to correct these errors by performing electrophysiological studies on the patient undergoing functional neurosurgery, kept awake during the procedures.
Intraparenchymal catheters may be guided to their targets in the brain using stereotactic techniques. Typically, stereotactic localization of a brain target is accomplished by fixing the stereotactic base ring to the skull and identifying the position of the target using imaging techniques. The position of the target is identified using three dimension co-ordinates by making measurements from radio-opaque fiducials attached to the stereotactic base ring. The stereotactic base ring may then be used as a platform from which to guide instruments to the target using a stereoguide on the stereotactic base ring that is set to the measured co-ordinates. The catheter may then be guided towards the target through the brain tissue after rigidifying it by the insertion of a stiff wire through its bore. Alternatively, a straight wire may be guided to the target first, and the catheter introduced around the wire so that one end (i.e. the inserted or distal end) is located within the brain, and the opposite end (i.e. the external or proximal end) remains outside the brain. Once positioned, the external end of the catheter can be fixed to the skull, and connected to a pump whereby the therapeutic agent may be administered. It will be appreciated that the outer diameter of the catheter tubing should be as small as possible, particularly when especially sensitive parts of the brain are to be treated, such as the mesencephalic targets, and are therefore to be passed through by the catheter. Such highly sensitive regions of the brain tend to be located in deep positions typically between 70 and 100 mm from the surface of the skull, such as the brain stem. Of course, the thinner the catheter tubing, the greater the deflection during insertion to those deep targets within the brain, and the increased likelihood that placement will be sub-optimal.